B淋巴细胞刺激因子对慢性特发性荨麻疹患者产生抗FcεRI抗体和抗IgE抗体的影响

【摘要】 目的 探讨B淋巴细胞刺激因子（BlyS）能否刺激慢性特发性荨麻疹（CIU）患者B淋巴细胞产生抗FcεRI抗体或抗IgE抗体。 方法 设CIU患者组和健康对照组。ELISA法测定血清中BlyS、抗FcεRI抗体和抗IgE抗体水平,分离培养受试者外周血B淋巴细胞,在培养液中加入BlyS,检测培养液中抗FcεRI抗体和抗IgE抗体水平,分析BlyS与抗FcεRI抗体和抗IgE抗体产生的相关性。结果 CIU患者血清BlyS水平显著高于健康对照组（t = 3.04,P < 0.01）,抗FcεRI抗体和抗IgE抗体水平均显著高于健康对照组（t = 3.51,P < 0.01;t = 3.29,P < 0.01）。CIU患者血清中抗FcεRI抗体和抗IgE抗体水平与BlyS水平呈正相关（r = 0.93,P < 0.01;r = 0.91,P < 0.01）;CIU患者外周血B淋巴细胞培养液中加入有效浓度BlyS后,B淋巴细胞培养液中抗FcεRI抗体和抗IgE抗体水平均显著高于不加BlyS的空白对照 （t = 3.67,P < 0.01;t = 3.56,P < 0.01）,2种抗体在培养液中的水平与BlyS浓度呈正相关（r = 0.96,P < 0.01;r = 0.91,P < 0.01）;抗FcεRI抗体和抗IgE抗体在CIU患者血清与培养液中的检出符合率分别为94.76%和87.84%。 结论 CIU患者血液中BlyS水平增高可刺激B淋巴细胞产生抗FcεRI抗体或抗IgE抗体,可能与CIU发病有关。 【关键词】 荨麻疹; B淋巴细胞刺激因子; 抗体,FcεRI; 抗体,IgE; B淋巴细胞     

荨麻疹

20140756 B淋巴细胞刺激因子对慢性特发性荨麻疹患者产生抗TeεRI抗体和抗IgE抗体的影响/康尔恂（青岛大学医学院附属烟台毓璜顶医院皮肤科）,李杰,孙丽伟…∥中华皮肤科杂志.-2013,46（10）.-707-710 设立CIU（慢性特发性荨麻疹患者）组和健康对照组。ELISA法测定血清中B淋巴细胞刺激因子（BlyS）、抗FcεRI抗体和抗IgE抗体水平;分离培养受试者外周血B淋巴细胞，在培养液中加入BlyS，检测培养液中抗FeεRI抗体和抗IgE抗体水平，分析BlyS与抗FεCRI抗体和抗IgE抗体产生的相关性。     

抗幽门螺杆菌抗体阳性慢性荨麻疹患者血清对人皮肤肥大细胞释放组胺作用的研究

【摘要】 目的 探讨抗幽门螺杆菌（Hp）抗体与慢性荨麻疹（CU）发病的关系。 方法 选择13C呼吸实验阳性、抗Hp抗体阳性的CU患者为实验组,健康人为对照组。用CU患者血清孵育人皮肤肥大细胞原代细胞株（HMC）,检测血清是否可刺激HMC细胞释放组胺。用抗Hp抗体（IgG）刺激HMC细胞,检测其是否具有活化细胞释放组胺的作用。检测CU患者血清中是否也含有高亲和力受体（FcεRI）抗体或抗IgE抗体。分别用抗FcεRI抗体、抗IgE抗体刺激HMC细胞,检测其活化HMC细胞释放组胺作用。 结果 CU患者组血清活化HMC细胞释放组胺作用（3.13 ± 0.93）高于健康对照组（2.92 ± 0.75,t = 2.39,P < 0.05）,4例CU患者血清中同时存在抗FcεRI抗体、3例存在抗IgE抗体。分别用这两种抗体阳性的CU患者血清孵育HMC细胞,释放组胺量均高于健康对照组（t值分别为4.82、6.34,均P < 0.01）,但用只含有抗Hp抗体CU患者血清孵育HMC细胞无释放组胺作用（与健康对照组比较,t = 1.74,P > 0.05）。抗Hp抗体（IgG）无激活HMC细胞释放组胺作用（与阴性对照血清比较,t = 1.95,P > 0.05）,抗FcεRI抗体、抗IgE抗体均可激活HMC细胞释放组胺（与阴性对照血清比较,t值分别为3.72、3.02,均P < 0.01）。 结论 抗Hp抗体对CU无致病作用,血清中同时存在抗FcεRI抗体或抗IgE抗体可导致部分Hp感染者同时患有CU。     

慢性荨麻疹患者自体血清皮肤试验与抗FcεRI抗体的关系分析

目的:了解慢性荨麻疹患者自体血清皮肤试验(ASST)与血清抗FcεRI抗体的关系.方法:对病例组56例慢性荨麻疹患者进行ASST,同时采用酶联免疫吸附试验法(ELISA)检测血清抗FcεRI抗体水平,并与对照组24名正常人比较.结果:病例组ASST阳性率为55 4%,血清抗FcεRI抗体水平为(2 89±2 36) U/L,两者均高于对照组(P<0 01);ASST阳性与阴性慢性荨麻疹患者血清抗FcεRI抗体水平分别为(3 23±2 62) U/L和(2 18±1 84) U/L,两者差异有统计学意义(P<0 05).结论:慢性荨麻疹患者ASST与抗FcεRI抗体水平有关,ASST阳性慢性荨麻疹患者血清抗FcεRI抗体水平较高.     

慢性荨麻疹患者自体血清皮肤试验与抗FcεRI抗体的关系分析

目的:了解慢性荨麻疹患者自体血清皮肤试验(ASST)与血清抗FcεRI抗体的关系.方法:对病例组56例慢性荨麻疹患者进行ASST,同时采用酶联免疫吸附试验法(ELISA)检测血清抗FcεRI抗体水平,并与对照组24名正常人比较.结果:病例组ASST阳性率为55 4%,血清抗FcεRI抗体水平为(2 89±2 36) U...     

慢性荨麻疹患者血清中抗FcεRⅠα自身抗体及其功能性的检测

目的:了解慢性荨麻疹患者血清抗FcεRⅠα自身抗体的阳性率,探讨慢性荨麻疹患者血清中组胺释放活性与抗FcεRⅠα自身抗体的关系。方法:以FcεRIα融合蛋白(rsFcεRⅠα)为抗原,用ELISA和免疫印迹法检测慢性荨麻疹患者血清中抗FcεRIα自身抗体,并通过抗FcεRⅠα自身抗体对组胺释放活性的影响证实其功能。结果:62例慢性荨麻疹患者中检出抗FcεRⅠα自身抗体阳性者22例(35.5%),其血清引起的组胺释放率平均为26.26%±16.08%;将其血清与rsFcεRⅠα作用后组胺释放率下降为9.14%±5.79%,组胺释放活性明显受到抑制。结论:部分慢性荨麻疹患者血清中的组胺释放活性因子与其血清中的抗FcεRIα自身抗体有关,抗FcεRⅠα自身抗体可能直接活化肥大细胞,释放组胺等血管活性介质,引起荨麻疹的发生。     

慢性荨麻疹和酒渣鼻患者血清中幽门螺杆菌抗体的检测与评价

目的检测慢性荨麻疹患者和酒渣鼻患者血清中的抗HP IgG抗体.方法采用AssureTM H.pylori IgG抗体层析板测定慢性荨麻疹和酒渣鼻患者血清中的抗HP IgG抗体,并设立正常对照组.结果186例慢性荨麻疹患者血清中有121例抗HP IgG抗体阳性,阳性率为65.05%,其中有88例提示为现症感染;38例酒渣鼻患者血清中有32例抗HP IgG抗体阳性,阳性率为84.21%,其中有21例提示为现症感染;正常对照组血清40例有11例抗HPIgG抗体阳性,阳性率为27.50%.结论慢性荨麻疹组患者血清中抗HPIgG抗体阳性率为65.05%,明显高于正常对照组27.50%(P＜0.01);酒渣鼻组患者血清中抗HP IgG抗体阳性率为84.21%,也明显高于正常对照组27.50%(P＜0.01).     

慢性特发性荨麻疹与幽门螺杆菌关系和治疗的研究

目的探讨慢性特发性荨麻疹(chronic idiopathic urticaria,CIU)与幽门螺杆菌(Helicobacter pylori,HP)关系及其治疗效果.方法 300例CIU患者进行14碳-尿素呼气试验(14C urea-breath test,14C-UBT),176例HP阳性者随机分为三组,其中58例予抗过敏治疗、59例抗过敏联合三联疗法治疗、59例中药联合三联疗法治疗,观察内容包括瘙痒、风团数量、风团大小、风团持续时间,比较各组治疗效果、分析CIU与HP之间关系.另外57例CIU患者进行自身血清抗体检测,其中35例HP阳性者予抗过敏联合三联疗法治疗,相同治疗方法与呼气试验组比较转阴率.108例健康体检者作为对照(其中65例进行呼气试验,43例血清抗体检测),以便对HP阳性率进行分析.结果CIU患者HP阳性率明显高于健康组(P＜0.01).联合三联疗法(抗过敏联合三联疗法、中药联合三联疗法)与单纯抗过敏治疗相比,治疗效果明显优于后者(P＜0.05),转阴率也明显高于后者(P＜0.01).治疗后HP转阴与未转阴患者疗效比较,前者明显优于后者(P＜0.05).结论 CIU与幽门螺杆菌关系密切,中药联合三联疗法治疗CIU效果好.     

抗FcεRⅠα自身抗体在慢性自发性荨麻疹中的表达及临床意义

目的研究抗FcεRⅠα自身抗体在慢性自发性荨麻疹(Chronic spontaneous urticaria,CSU)中的表达及临床意义。方法采用酶联免疫吸附法(ELISA)检测CSU患者中抗FcεRⅠα自身抗体的表达,并分析抗FcεRⅠα自身抗体与CSU患者的病程、荨麻疹活动性评分(UAS)评分、风团数目、瘙痒程度、生活质量评分、单一抗组胺药疗效的临床相关性。结果 CSU患者组抗FcεRⅠα抗体水平较正常对照组明显升高(P0.05),抗FcεRⅠα抗体水平与病程、荨麻疹活动性评分(Urticaria activity score,UAS)、风团数目评分、瘙痒程度评分、生活质量评分无明显相关性(P0.05),单一抗组胺药使用有效者其血清抗FcεRⅠα抗体滴度低于单一抗组胺药治疗无效者(P0.05)。结论抗FcεRⅠα抗体在CSU发病中有重要的作用,抗FcεRⅠα抗体滴度较高的CSU患者可能对常规抗组胺药治疗抵抗。     

自体血清皮肤试验对诊断慢性荨麻疹的临床意义

目的 探讨慢性荨麻疹自体血清皮肤试验（ASST）的不同红斑风团反应读出结果与患者血清激发嗜碱粒细胞组胺释放和血清IgG型抗高亲和力IgE Fc受体α链（抗Fc?着RI）自身抗体含量的关系。方法 60例患者均符合慢性荨麻疹的诊断标准,ASST试验阳性结果判定参照Sabroe报告的标准,又依据红斑风团反应不同,进一步将Sabroe标准ASST阳性分为风团 + 红斑模式和单纯风团模式,将Sabroe标准ASST阴性分为单纯红斑模式与无反应模式。采用酶联免疫吸附试验（ELISA）对患者血清激发正常人外周血嗜碱粒细胞组胺释放能力和血清中抗Fc?着RI自身抗体含量进行测定。结果 60例慢性荨麻疹患者ASST测试阳性19例（31.7%）,其中表现风团 + 红斑模式16例和风团模式3例;ASST阴性41例,其中无反应模式38例和红斑模式3例。慢性荨麻疹患者ASST阳性血清刺激嗜碱粒细胞组胺释放率（33.83% ± 9.83%）较ASST阴性血清（4.06% ± 1.44%）显著升高（t = 5.13,P < 0.01）,且几乎是10 μmol/L趋化三肽（18.67% ± 1.77%）的2倍。仅ASST阳性（风团和红斑模式）的血清能检出高滴度的抗Fc?着RI自身抗体（757.64 ± 168.99 ng/L）,正常对照血清自身抗体含量仅为43.25 ± 16.63 ng/L。结论 ASST阳性（风团和红斑模式）提示血清中含有高滴度的抗Fc?着RI自身抗体,可考虑自身免疫性慢性荨麻疹的临床诊断。     

Correlations between Anti-Mast Cell Autoantibodies and Chronic Idiopathic Urticaria

Background

The etiology of chronic idiopathic urticaria (CIU) is not completely clear. There are a few antibodies were reported to correlate with CIU.

Objective

To investigate the correlation these antibodies and CIU.

Methods

The autologous serum skin test (ASST) and allergens were performed. Serum levels of immunoglobulin E (IgE), anti-FcεRI and anti-IgE, anti-Helicobacter pylori (HP) antibodies and anti-thyroglobulin antibody (TGAb) were measured in 100 patients with CIU, acute urticaria (AU) and normal controls respectively.

Results

Eighty-six percent food or inhalant allergens were detected in AU patients, but no allergens were detected in CIU patients and normal controls. Serum anti-FcεRI antibody and anti-IgE antibody levels were higher in the CIU than that in the AU patients and normal controls (p<0.05, respectively). IgE level was lower in the CIU patients (T=190.00, p< 0.05), but increased in the AU patients (T=226.00, p<0.05) compared with the normal controls. The ASST positive rates in the CIU and the AU patients were 53.4% and 12.6% respectively, but all normal controls were negative. The anti-FcεRI antibody level was higher in the ASST-positive CIU patients than those negative ones (T=101.73, p<0.05). In anti-HP antibody positive and TGAb positive CIU patients, anti-FcεRI antibody positive rate was higher than AU patients (p<0.01) and normal controls (p<0.01).

Conclusion

The anti-FcεRI and anti-IgE antibodies play a key role in CIU, but anti-HP antibody and TGAb have an indirect correlation with CIU.     

The autologous serum skin test in a cohort of chronic idiopathic urticaria patients compared to respiratory allergy patients and healthy individuals

BACKGROUND: A positive autologous serum skin test (ASST) is considered to reflect the presence of anti-FceRI and/or anti-IgE autoantibodies that are capable of activating mast and basophil cell degranulation. The ASST is regarded as a reliable in vivo test in chronic idiopathic urticaria (CIU) patients, with diagnostic, therapeutic and prognostic implications. However, positive ASST results have also occasionally been demonstrated in patients with other diseases and in healthy subjects. OBJECTIVE: To evaluate the specificity and sensitivity of the ASST in a cohort of CIU patients compared to a cohort of respiratory-allergic patients and a group of normal individuals. METHODS: ASST was performed in a cohort of 116 subjects, 47 subjects with seasonal allergic rhinitis, 32 respiratory-symptom-free CIU patients, and 37 healthy individuals. RESULTS: The results were compared statistically to those of the CIU patients. The intradermal injection of autologous serum induced a weal and flare reaction in 17/32 (53.1%) CIU patients; 14/47 (29.8%) patients with seasonal allergic rhinitis (P=0.06) and in 15/37 (40.5%) of the healthy controls (P=0.34). The sensitivity and specificity of the ASST in the CIU patients and the seasonal allergic rhinitis patients was 53 and 28%, respectively. When comparing the CIU patients with the healthy controls the sensitivity and specificity was 55 and 31%, respectively. The positive and negative predictive values of the ASST when comparing CIU patients with healthy controls were 53 and 59.5%, respectively. The positive and negative predictive values of the ASST in the CIU patients compared to seasonal allergic rhinitis patients were 53 and 70%, respectively. CONCLUSION: The relatively low sensitivity and specificity of the ASST in the CIU patients compared to the seasonal allergic rhinitis patients and healthy controls warrants a more critical interpretation of the ASST in chronic idiopathic urticaria.     

慢性荨麻疹患者外周血中CD8~+CD28~-T细胞检测结果分析

目的:探讨CD8~+CD28~-T细胞在慢性荨麻疹患者致病机制中的作用。方法:收集临床慢性荨麻疹(CU)病例83例,同时设立对照组64例进行比较。应用ELISA法检测研究对象血清中抗Ig E抗体、抗FcεRⅠ抗体浓度,流式细胞仪检测外周血中CD3~+、CD4~+、CD8~+、CD8~+CD28~-、CD4~+CD25~+T细胞比例,分析检测结果。结果:83名CU中,23例抗Ig E抗体为阳性,占27.7%(27/83);31例抗FcεRⅠ抗体为阳性,占37.3%(31/83)。CU患者外周血CD8~+T细胞比例、CD8~+CD28~-T细胞比例低于正常对照组(P0.05),CD4~+/CD8~+比值、CD4~+CD25~+T细胞比例均高于对照组(P0.05)。结论:CU患者机体外周血CD8~+CD28~-T细胞、CD4~+CD25~+T细胞比例与对照组相比存在差异,CD8~+CD28~-T细胞比例降低也可能是CU致病机制之一。     

Evaluation of autologous serum skin test results in patients with chronic idiopathic urticaria, allergic/non-allergic asthma or rhinitis and healthy people

Background. Recent data indicate that the autologous serum skin test (ASST) shows a high rate of reactivity not only in chronic idiopathic urticaria (CIU) but also in cases with non‐allergic asthma and rhinitis (NAAR), multiple drug allergy syndrome (MDAS) and even in some healthy people. Aim. To evaluate ASST reactivity in patients with CIU, allergic/non‐allergic asthma or rhinitis and in healthy controls. Methods. We studied 80 patients with CIU, 40 non‐atopic patients with NAAR, 57 patients with allergic rhinitis (AR) and allergic bronchial asthma (ABA), and 45 healthy controls. ASST was performed in all patients and controls, and it was considered positive when a serum‐induced weal with a diameter 1.5 mm greater than the negative (saline) control, surrounded by erythema, was present. Results. In total, 42 patients with CIU showed ASST reactivity (52.5%). ASST was found to be positive in 8 of 40 patients with NAAR (20%). The rate was similar (17.5%) in the AR/ABA patient group. However, 25 healthy controls (55.5%) also had positive ASST. The highest rate was in female controls and in individuals in the 18–30‐year‐old age group. Conclusion. The data indicate that ASST positivity might be a nonspecific phenomenon, influenced by many factors. In the light of the results of this study, we suggest that the significance of ASST reactivity should be re‐evaluated in CIU. In addition, the importance of ASST reactivity in patients with AR/ABA and in patients with NAAR remains unclear, and further controlled studies are needed.     

Activated status of basophils in chronic urticaria leads to interleukin-3 hyper-responsiveness and enhancement of histamine release induced by anti-IgE stimulus

BACKGROUND: Basophils and mast cells are the main target cells in chronic idiopathic urticaria (CIU). Besides the basopenia, intrinsic defects of the anti-IgE cross-linking signalling pathway of basophils have been described in CIU. OBJECTIVES: We sought to investigate the profile of expression of activation markers on basophils of patients with CIU and to explore the effect of interleukin (IL)-3 priming upon anti-IgE cross-linking stimuli through expression of activation markers and basophil histamine releasability. METHODS: Evaluation of the surface expression of FcepsilonRIalpha, CD63, CD203c and CD123 on whole blood basophils of patients with CIU undergoing autologous serum skin test (ASST) was performed by flow cytometry. The effect of pretreatment with IL-3 in the anti-IgE response was analysed by the expression of basophil activation markers and histamine release using enzyme-linked immunosorbent assay. RESULTS: Blood basophils of patients with CIU were reduced in number and displayed increased surface expression of FcepsilonRIalpha, which was positively correlated with the IgE serum levels. Upregulation of expression of both surface markers CD203c and CD63 was verified on basophils of patients with CIU, regardless of ASST response. High expression of IL-3 receptor on basophils was detected only in ASST+ patients with CIU. Pretreatment with IL-3 upregulated CD203c expression concomitantly with the excreting function of blood basophils and induced a quick hyper-responsiveness to anti-IgE cross-linking on basophils of patients with CIU compared with healthy controls. CONCLUSIONS: Basophils of patients with CIU showed an activated profile, possibly due to an in vivo priming. Functionally, basophils have high responsiveness to IL-3 stimulation, thereby suggesting that defects in the signal transduction pathway after IgE cross-linking stimuli are recoverable in subjects with chronic urticaria.     

Autologous whole blood injections to patients with chronic urticaria and a positive autologous serum skin test: a placebo-controlled trial

BACKGROUND: Patients with chronic urticaria (CU) frequently exhibit positive skin test reactions to autologous serum (ASST). Therapies aimed at inducing tolerance to circulating histamine-releasing factors in ASST+ CU patients, e.g. by treatment with autologous whole blood (AWB), have not yet been tested. OBJECTIVE: To test whether ASST+ CU patients can benefit from repeated low-dose intramuscular injections of AWB. METHODS: We characterized CU severity and duration, anti-Fc(epsilon)RI and anti-IgE expression, use of antihistamines, and quality of life in 56 CU patients (ASST+: 35, ASST-: 21) and assessed the therapeutic effects of 8 weekly AWB injections in a randomized, placebo-controlled, single-blind, parallel-group trial. RESULTS: Numbers, size, intensity, and/or duration of CU symptoms, quality of life, as well as expression of anti-Fc(epsilon)RI or anti-IgE were similar in ASST+ and ASST- CU patients. However, CU in ASST+ patients was of longer duration and required markedly more antihistaminic medication. Interestingly, ASST+ patients, but not ASST- patients, showed significantly (1) reduced CU activity, (2) decreased use of antihistamines, and (3) improved quality of life after AWB treatment. Placebo treatment was ineffective in both groups, but differences of AWB and placebo treatment responses did not achieve statistical significance in either group, most likely due to the limited number of patients treated. CONCLUSION: Our findings suggest that ASST+ CU is clinically different from other CU subforms and that ASST+ CU patients can benefit from AWB therapy.     

慢性特发性荨麻疹患者自体血清皮肤试验结果分析

目的：探讨慢性特发性荨麻疹(CIU)患者自体血清皮肤试验临床应用的意义。方法：对30例CIU患者及lO名正常对照者做自体血清皮肤试验，并对结果进行比较分析。结果：30例CIU患者自体血清皮肤试验阳性率为30％(9／30)，而对照组全部阴性。结论：部分CIU患者血清中有功能性的循环自身抗体存在，自体血清皮肤试验可作为CIU自身抗体的过筛试验。